Methods for promoting hair growth

ABSTRACT

The present invention relates to methods of promoting hair growth in a patient. The method comprises administering to a patient in need thereof a sugar compound that is converted to a glycosaminoglycan in the patient, a primary antioxidant component, at least one amino acid component, and one or more transition metals.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 10/400,795,filed Mar. 28, 2003 now U.S. Pat. No. 7,452,527, now allowed, thecontents of which are incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

The invention relates to methods of promoting hair growth in a patientin need thereof by administering to the patient a sugar compound that isconverted to a glycosaminoglycan in the patient, a primary antioxidantcomponent, at least one amino acid component, and one or more transitionmetals.

BACKGROUND

The human scalp normally harbors 100,000 to 150,000 hair follicles orhairs. The hair follicles or hair roots are the hair-forming organs. Thelong, strong, hairs, which build up the hair coverage of the head, arereferred to as terminal hairs. The very fine, very short hairs, barelyprotruding over the surface of the skin, at the edges of the haircoverage on the head are referred to as fuzz hair, or vellus hair.

The growth of hair is not continuous, but cyclical. Three growth phasesare identified: (1) the anagen phase, (2) the catagen phase, and (3) thetelogen phase. The anagen phase is the period of active hair growth and,insofar as scalp hair is concerned, generally lasts from 3-5 years. Thecatagen phase is a short transitional phase between the anagen and thetelogen phases, which, in the case of scalp hair, lasts only 1-2 weeks.The telogen phase is essentially a quiescent or resting phase where allgrowth ceases and the hair eventually is shed prior to the commencementof a new growth cycle. Scalp hair in the telogen phase is alsorelatively short-lived, some 3-4 months elapsing before the hair is shedand a new hair begins to grow. The hair of the head is thus underconstant renewal. At any given time approximately 88% of the hairs arein the anagen phase, 1% are in the catagen phase, and the remainder arein the telogen phase.

Dermatologists recognize many different types of hair loss, the mostcommon by far being “alopecia,” or male pattern baldness, in whichhumans, typically males, begin losing scalp hair at the temples and onthe crown of the head as they get older. While this kind of hair loss islargely confined to males, it is not unknown in women. Other types ofhair loss, which can be considerable, temporary or permanent, can beinduced by poor nutrition; emotional stress; hormone imbalance; ormedicinal drugs, such as cancer chemotherapy agents. These disorders andthe mechanisms that produce them are poorly understood. Nevertheless,they are common and distressing, since hair is an important factor inhuman social and sexual communication.

U.S. Pat. No. 4,596,812 to Chidsey III et al. discloses a method fortreating alopecia which comprises regular topical application of thecompound 2,4-diamino-6-piperidino-pyrimidine 3-oxide or “Minoxidil.”

U.S. Pat. No. 5,523,078 to Baylin discloses an aqueous composition forthe treatment of hair and scalp which includes a chelating agent, gellangum, a vitamin precursor, a preservative, biotin, a vitamin derivative,gamma-linolenic acid, menthol, a liposome, a conditioner, a solubilizer,a conditioner/humectant, folic acid, and a poly amino sugar condensate.

U.S. Pat. No. 6,465,514 to Hallam discloses compositions consistingessentially of procaine hydrochloride, niacin and minoxidil. Thecompositions are allegedly useful for promoting hair growth.

U.S. Pat. No. 6,511,659 to Mahe et al. discloses pyrimidine 3-oxidecompounds allegedly useful for inducing/stimulating hair growth orretarding hair loss.

U.S. Pat. No. 6,271,246 to Murad discloses pharmaceutical compositionsconsisting essentially of an acidic component comprising a hydroxy acidor tannic acid, a niacin component, and a 5-α reductase inhibitor. Thecompositions are useful for managing scalp conditions such as thinninghair.

U.S. Pat. No. 5,804,594 to Murad discloses pharmaceutical compositionsuseful for improving wrinkles and other skin conditions. Thecompositions include a sugar compound that is converted toglycosaminoglycan in the patient, a primary antioxidant component, atleast one amino acid component, and at least one transition metalcomponent.

Despite attempts in the pharmaceutical and cosmetic industry to developcompositions to promote hair growth and reduce alopecia, no widelyaccepted solution exists. Moreover, many of the proposed solutionspresent unwanted side effects. Hence, there is still a need foreffective and safe compositions to promote hair growth.

SUMMARY OF THE INVENTION

The present invention relates to methods of promoting hair growth in apatient in need thereof. The method comprises administering to thepatient (i) a sugar compound that is converted to a glycosaminoglycan inthe patient, (ii) a primary antioxidant component, (iii) at least oneamino acid component, and (iv) at least one transition metal component.

DETAILED DESCRIPTION

Applicants have discovered that administering to a patient (i) a sugarcompound that is converted to a glycosaminoglycan in the patient, (ii) aprimary antioxidant component, (iii) at least one amino acid, and (iv)at least one transition metal component (collectively “the hair growthcomponents”) promotes hair growth in the patient.

In one embodiment, the patient is a mammal. In another embodiment, thepatient is a human.

The method involves administering a sugar compound that is converted toa glycosaminoglycan in the patient. In one embodiment, the sugarcompound is N-acetyl glucosamine, D-glucosamine sulfate, or chondroitinsulfate. In a preferred embodiment, the sugar compound is apharmaceutically acceptable salt or ester of N-acetylglucosamine. In amore preferred embodiment, the sugar compound is N-acetylglucosamineitself. Typically, the daily dose of the sugar component is from about40 mg to about 2500 mg per day, preferably from about 60 mg to about1000 mg per day, and more preferably from about 100 mg to about 300 mgper day.

The primary antioxidant is typically a vitamin C source. Preferably, theprimary antioxidant is ascorbic acid, or a pharmaceutically acceptablesalt or ester thereof, and more preferably is ascorbyl palmitate;dipalmitate L-ascorbate; sodium L-ascorbate-2-sulfate; or an ascorbatesalt, such as sodium, potassium, or calcium ascorbate; or mixturesthereof. Typically, the daily dose of the primary antioxidant source isfrom about 40 mg to about 2400 mg per day, preferably from about 60 mgto about 600 mg per day, and more preferably from about 80 to about 300mg per day. Vitamin C, the typical primary antioxidant for the method,is approved by the FDA and has wide consumer acceptance, so that it canbe used in amounts as high as 10,000 mg, if desired. When oralformulations of the pharmaceutical composition are used, it is preferredthat a non-acidic form of vitamin C be used to reduce stomach irritationthat may occur when using an acidic form.

The method also involves administering at least one amino acid.Preferably, two or more amino acids are administered in combination.Either the L- or D-forms of amino acids are acceptable. Lysine andproline are the most preferred amino acids and are advantageously usedin combination. Cysteine, methionine or other amino acids can also beused, if desired. A useful source of the amino acid cysteine is N-acetylcysteine and a useful source of the amino acid methionine isL-selenomethionine, wherein the selenium component is between about 0.1to about 3 weight percent of the methionine source. The amino acids maybe administered in a soluble form such as a salt, for example, ahydrochloride salt such as L-Lysine hydrochloride. Typically, the dailydose for each amino acid is from about 35 mg per day to about 1200 mgper day, preferably from about 50 mg per day to about 600 mg per day,and more preferably from about 70 mg per day to about 400 mg per day.

The method also involves administering one or more transition metals.Preferably the transition metal is zinc, manganese, copper, orcombinations thereof. The combinations are most preferred. Typically,the daily dose of the transition metal component is from about 4.1 mg toabout 740 mg per day, more preferably from about 8.2 mg to about 370 mgper day, and most preferably from about 20 mg to about 150 mg per day.In one embodiment, the one or more transition metals are a combinationof zinc and manganese. In another embodiment, the one or more transitionmetals are a combination of zinc and copper. In another embodiment, theone or more transition metals are a combination of manganese and copper.In another embodiment, the one or more transition metals are acombination of zinc, manganese, and copper.

When the transition metal comprises zinc, the zinc may be any zinccompound or pharmaceutically acceptable salt thereof. In one embodiment,the zinc is complexed with an amino acid. In one embodiment, the zinc ispresent as zinc monomethionine, wherein the zinc is present in an amountof from about 10 to about 30 weight percent of the complex.

When the transition metal comprises manganese, the manganese may be anymanganese compound or pharmaceutically acceptable salt thereof. In oneembodiment, the manganese is at least partially complexed with a vitaminC source, wherein the manganese is present in an amount of from about 5to 20 weight percent of the complex. When complexed with vitamin C, thevitamin C source may be included in the overall percentage of vitamin Cused as the primary antioxidant in the method. In one embodiment, themanganese is present as manganese ascorbate or manganese ascorbic acid.

When the transition metal comprises copper, the copper may be any coppercompound or pharmaceutically acceptable salt thereof. In one embodiment,the copper is present as copper sebacate, wherein the copper is presentin an amount of from about 5 to about 20 weight percent of the coppersebacate.

In one embodiment, the hair growth components are administeredsequentially.

In another embodiment, the hair growth components are administeredconcurrently, for example as a composition comprising each of the hairgrowth components.

When the hair growth components are administered sequentially, the timespan between the administration of each ingredient typically ranges fromabout 1 minute to about 1 day. In this embodiment, the hair growthcomponents can be administered in any order.

When the hair growth components are administered concurrently, they canbe administered as a composition (“the hair growth composition”) thatcomprises each of the sugar compound that is converted to aglycosaminoglycan in the patient, the primary antioxidant component, theat least one amino acid, and the transition metal component. In oneembodiment, the hair growth composition may be administered as a singledose once per day. In another embodiment, the dose is divided andadministered from about 1 to about 10 times per day, preferably about 2to 6 times per day, and more preferably about 4 times per day. The term“dose” is meant to describe a daily dose.

The sugar compound that is converted to a glycosaminoglycan in thepatient is typically present in the hair growth composition in an amountof from about 5 to about 50 weight percent, preferably from about 10 toabout 40 weight percent, and more preferably from about 15 to about 30weight percent of the hair growth composition.

The primary antioxidant component is typically present in the hairgrowth composition in an amount of from about 5 to about 50 weightpercent, preferably from about 7 to about 40 weight percent, and morepreferably from about 10 to about 25 weight percent the hair growthcomposition.

The one or more amino acids are each typically present in the hairgrowth composition in an amount of from about 2 to about 25 weightpercent, preferably from about 4 to about 20 weight percent, and morepreferably from about 6 to about 15 weight percent of the hair growthcomposition. When the amino acid source is a cysteine source, such asN-acetyl cysteine, it is typically present in the hair growthcomposition in an amount of from about 1 to about 10 weight percent,preferably from about 2 to about 8 weight percent, and more preferablyfrom about 3 to about 6 weight percent of the hair growth composition.When the amino acid source is a methionine source, suchL-selenomethionine, it is typically present in the hair growthcomposition in an amount of from about 0.1 to about 5 weight percent,preferably from about 0.2 to about 3 weight percent, and more preferablyfrom about 0.3 to about 1 weight percent of the hair growth composition.

The transition metal components are present in the hair growthcomposition in an amount of from about 0.5 to about 15 weight percent ofthe hair growth composition. When the transition metal is zinc, the zincis typically present in an amount of from about 1 to about 10 weightpercent, more preferably about 2 to about 7 weight percent and mostpreferably about 3 to about 5 weight percent of the hair growthcomposition. When the transition metal is manganese, the manganese istypically present in the hair growth composition in an amount of fromabout 1 to about 10 weight percent, preferably about 2 to about 7 weightpercent, and more preferably about 2.5 to about 4 weight percent of thehair growth composition. When the transition metal is copper, the copperis typically present in the hair growth composition in an amount of fromabout 0.1 to about 5 weight percent, preferably about 0.2 to about 3weight percent, and more preferably about 0.3 to about 1 weight percentof the hair growth composition.

The term “pharmaceutically acceptable salt”, as used herein, refers to asalt prepared from pharmaceutically acceptable non-toxic acids or basesincluding inorganic or organic acids. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, sulfuric, and phosphoric.Appropriate organic acids may be selected, for example, from aliphatic,aromatic, carboxylic and sulfonic classes of organic acids, examples ofwhich are formic, acetic, propionic, succinic, glycolic, glucuronic,maleic, furoic, glutamic, benzoic, anthranilic, salicylic, phenylacetic,mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic,pantothenic, benzenesulfonic, stearic, sulfanilic, algenic, andgalacturonic. Examples of such inorganic bases, for potential saltformation with the sulfate or phosphate compounds of the invention,include metallic salts made from aluminum, calcium, lithium, magnesium,potassium, sodium, and zinc. Appropriate organic bases may be selected,for example, from N,N-dibenzylethylenediamine, chloroprocaine, choline,diethanolamine, ethylenediamine, meglumaine (N-methylglucamine), andprocaine.

In addition to the hair growth components, the method of the inventionmay further involve administering one or more optional additives. In oneembodiment, the method further involves administering a catechin-basedpreparation, along with glucosamine or a pharmaceutically acceptablesalt or ester thereof, and chondroitin or a pharmaceutically acceptablesalt or ester thereof.

The catechin-based preparation is preferably a proanthanol orproanthocyanidin, more preferably a proanthocyanidin, and mostpreferably grape seed extract. These compounds are considered to besecondary antioxidants, because they are present in lesser amounts thanthe primary antioxidant. A daily dose of the catechin-based preparationis typically from about 5 mg to about 2250 mg per day, more preferablyfrom about 7.5 mg to about 500 mg per day, and most preferably fromabout 10 mg to about 50 mg per day. When the catechin-based preparationis included in the hair growth composition, the catechin-basedpreparation is typically present in an amount of from about 0.5 to about5 weight percent, more preferably from about 0.6 to about 3 weightpercent, and most preferably from about 0.7 to about 2 weight percent ofthe hair growth composition.

The typical dose for the glucosamine or a pharmaceutically acceptablesalt or ester thereof is from about 10 mg to about 1500 mg per day, morepreferably from about 50 to about 750 mg per day, and most preferablyfrom about 100 to about 200 mg per day. The typical dose for thechondroitin or a pharmaceutically acceptable salt or ester thereof isfrom about 10 mg to about 1500 mg per day, more preferably from about 50to about 750 mg per day, and most preferably from about 100 to about 200mg per day. When the glucosamine or a pharmaceutically acceptable saltor ester thereof and the chondroitin or a pharmaceutically acceptablesalt or ester thereof are included in the hair growth composition, theglucosamine or a pharmaceutically acceptable salt or ester thereof, andthe chondroitin or a pharmaceutically acceptable salt or ester thereofare each typically present in an amount of from about 3 to about 17weight percent, preferably from about 4 to about 12 weight percent each,and more preferably from about 5 to about 8 weight percent of the hairgrowth composition. In one embodiment, the glucosamine or apharmaceutically acceptable salt or ester thereof is present as asulfate or succinate; preferably as D-glucosamine sulfate, wherein theglucosamine is present as about 60 to about 90 weight percent of thesalt. In another embodiment, the chondroitin is present as a sulfate orsuccinate; preferably as chondroitin sulfate, wherein the chondroitin ispresent as about 65 to about 95 weight percent of the salt.

The method may further involve administering one or more optionaladditives such as a vitamin E source, a vitamin B₃ source, quercetinpowder, pyridoxal 5 phosphate-Co B₆, or a vitamin A source.

In one embodiment, the method further involves administering a vitamin Esource. In one embodiment, the vitamin E source is a sulfate orsuccinate vitamin E complex. In another embodiment, the vitamin E sourceis D-alpha tocopheryl acid succinate. The dose for any of these vitaminE sources is typically from about 10 mg to about 800 mg per day, morepreferably from about 25 mg to about 400 mg per day, and most preferablyfrom about 40 mg to about 120 mg per day. The vitamin E source, however,should not be ingested in an amount higher than about 1,500 mg per day,as Vitamin E becomes toxic at higher doses. When the vitamin E source isincluded as part of the hair growth composition, the vitamin E source istypically present in an amount of from about 1 to about 15 weightpercent, preferably from about 2 to about 12 weight percent, and morepreferably from about 3 to about 10 weight percent of the hair growthcomposition.

In one embodiment, the method further involves administering a vitaminB₃ source. The dose for any vitamin B₃ source is typically from about 4mg to about 125 mg per day, preferably from about 10 mg to about 75 mgper day, and more preferably from about 20 mg to about 50 mg per day. Inone embodiment, the vitamin B₃ source is niacinamide. When the vitaminB₃ source is included as part of the hair growth composition, thevitamin B₃ source is typically present in an amount of from about 0.5 toabout 15 weight percent, preferably from about 1 to about 12 weightpercent, and more preferably from about 1.5 to about 10 weight percentof the hair growth composition.

In one embodiment, the method further involves administering a vitamin Asource. In one embodiment, the vitamin A dose is about 500,000 IU (or165 mg) per day. Vitamin A is toxic at high levels, such that no morethan 400,000 IU should be cumulatively ingested per day for greater thansix months. Preferably, the dose for any Vitamin A compound is fromabout 2 mg to about 20 mg per day, and more preferably from about 4 mgto about 10 mg per day. In one embodiment, the vitamin A source isvitamin A palmitate. When the vitamin A source is included in the hairgrowth composition, the vitamin A source is typically present in anamount of from about 0.1 to about 5 weight percent, preferably fromabout 0.2 to about 3 weight percent, and more preferably from about 0.3to about 1 weight percent of the hair growth composition.

In one embodiment, the method further involves administering quercetinpowder. The dose for quercetin powder is typically from about 4 mg toabout 125 mg per day, more preferably from about 10 mg to about 75 mgper day, and most preferably from about 20 mg to about 50 mg per day. Inone embodiment, the quercitin powder is quercetin dihydrate. Whenquercitin powder is included as part of the hair growth composition itis typically present in an amount of from about 0.5 to about 15 weightpercent, preferably from about 1 to about 12 weight percent, and morepreferably from about 1.5 to about 10 weight percent of the hair growthcomposition.

In one embodiment, the method further involves administering pyridoxal 5phosphate-Co B₆, also known as P-5-P monohydrate. The dose for pyridoxal5 phosphate-Co B₆ is typically from about 1 mg to about 40 mg per day,more preferably from about 2 mg to about 20 mg per day, and mostpreferably from about 4 mg to about 10 mg per day. When the pyridoxal 5phosphate-Co B₆ is included as part of the hair growth composition it istypically present in an amount of from about 0.1 to 5 weight percent,preferably from about 0.2 to 3 weight percent, and more preferably fromabout 0.3 to 1 weight percent of the hair growth composition.

In one embodiment, the method further involves administering one or moreof lecithin, phosphatidyl choline, or choline. The dose for lecithin istypically from about 10 mg to about 25,000 mg per day, more preferablyfrom about 25 mg to about 15,000 mg per day, and most preferably fromabout 50 mg to about 1,000 mg per day. When lecithin is included as partof the hair growth composition it is typically present in an amount offrom about 0.5 to about 75 weight percent, preferably from about 1.0 toabout 50 weight percent, and more preferably from about 1.5 to about 20weight percent of the hair growth composition. The dose for phosphatidylcholine is typically from about 1 mg to about 10,000 mg per day, morepreferably from about 10 mg to about 5,000 mg per day, and mostpreferably from about 20 mg to about 500 mg per day. When phosphatidylcholine is included as part of the hair growth composition it istypically present in an amount of from about 0.5 to about 50 weightpercent, preferably from about 1.0 to about 25 weight percent, and morepreferably from about 1.5 to about 10 weight percent of the hair growthcomposition. The dose for choline is typically from about 0.5 mg toabout 3,000 mg per day, more preferably from about 1 mg to about 500 mgper day, and most preferably from about 2 mg to about 50 mg per day.When choline is included as part of the hair growth composition it istypically present in an amount of from about 0.5 to about 25 weightpercent, preferably from about 1.0 to about 10 weight percent, and morepreferably from about 1.5 to about 5 weight percent of the hair growthcomposition. Without wishing to be bound by theory, Applicants believethat the combination of glycosaminoglycan and one or more of lecithin,phosphatidyl choline, or choline strengthens the cell membrane andincreases the water content of cells which improves hair growth.

In one embodiment, the method involves topical administration andfurther includes administering hydrogen peroxide. The hydrogen peroxideis administered in an amount sufficient to cleanse at least a portion ofthe skin. Preferably, the hydrogen peroxide is administered in an amountto cleanse the skin without substantial irritation. “Cleanse”, as usedherein, includes the removal of dirt, debris, air pollutants,desquamating cells, and cutaneous secretions of the skin. In oneembodiment, the hydrogen peroxide is topically administered as a 3%solution (by mass) to cleanse the skin before topically administeringthe hair growth components. When the hydrogen peroxide is included aspart of the hair growth composition it is typically present in an amountof from about 0.01 to about 6 weight percent, preferably from about 0.05to about 4 weight percent, and more preferably from about 0.1 to about 1weight percent of the hair growth composition. Without wishing to bebound by theory it is believed that cleansing the skin with hydrogenperoxide improves penetration into the skin of the topically appliedhair growth components.

In one embodiment, the method involves topical administration andfurther includes administering to the patient one or more moisturizingagents. “Moisturizing agent,” as used herein, is used to include anyagent that facilitates hydration of the skin by inhibiting or preventingloss of water from the skin, absorbing water from the atmosphere andhydrating the skin, or enhancing the skin's own ability to absorb waterdirectly from the atmosphere, or a combination thereof. Preferably, whenthe method involves administering a moisturizing agent, the moisturizingagent and the hair growth components are administered topically. Withoutwishing to be bound by theory it is believed that the moisturizing agentimproves the skin's ability to absorb topically administered hair growthcomponents. Moisturizing agents also minimize or prevent the skin fromdrying and cracking; cracked skin is more susceptible to environmentalfactors that generate free radicals, which are believed to damage theskin. Suitable moisturizing agents include, but are not limited to,hydrophobic agents, and hydrophilic agents, and combinations thereof.The dose for any of these moisturizing agents is typically from about0.1 mg to about 2000 mg per day, preferably from about 1 mg to about 500mg per day, and more preferably from about 5 mg to about 100 mg per day.When the moisturizers are included as part of the hair growthcomposition, the total amount of moisturizers are typically present inan amount of from about 0.01 to about 20 weight percent, preferably fromabout 0.05 to about 10 weight percent, and more preferably from about0.1 to about 5 weight percent of the hair growth composition.

Representative moisturizing agents that are hydrophobic moisturizingagents include, but are not limited to, ceramide, borage oil (linoleicacid), tocopherol (Vitamin E), tocopherol linoleate, dimethicone,glycerine, and mixtures thereof. Hydrophobic agents, when present, arebelieved to moisturize the skin by inhibiting or preventing the loss ofwater from the skin. The hydrophobic agent, when present in the hairgrowth composition, is typically present in an amount of from about 0.01to about 20 weight percent, preferably from about 0.05 to about 15weight percent, and more preferably from about 0.1 to about 5 weightpercent of the hair growth composition.

Representative moisturizing agents that are hydrophilic agents include,but are not limited to, hyaluronic acid, sodium peroxylinecarbolic acid(sodium PCA), wheat protein (e.g., laurdimonium hydroxypropyl hydrolyzedwheat protein), hair keratin amino acids, and mixtures thereof. Sodiumchloride may also be present, particularly when hair keratin amino acidsare included as a moisturizer. Hydrophilic agents, when present, arebelieved to moisturize the skin by absorbing moisture from theatmosphere to hydrate or facilitate hydration of the skin. Thehydrophilic agent, when present in the hair growth composition, istypically present in an amount of from about 0.01 to about 20 weightpercent, preferably from about 0.05 to about 15 weight percent, and morepreferably from about 0.1 to about 5 weight percent of the hair growthcomposition.

Other moisturizing agents that hydrate the skin and are useful in thecompositions and methods of the present invention include, but are notlimited to, panthenol; primrose oil; GLA 3 and other fish oils that mayinclude, for example, the omega-3 and omega-6 oils and/or linoleic acid;and flax seed oil.

In one embodiment, the method involves administering both a hydrophilicmoisturizing agent and a hydrophobic moisturizing agent. Without wishingto be bound by theory it is believed that the combination of ahydrophilic moisturizing agent and a hydrophobic moisturizing agentinteract in a synergistic manner to provide optimum conditions forabsorption by the skin of topically applied hair growth components.

In another embodiment, the method involves topical administration of thehair growth components and further includes administering an exfoliantto help remove dead or dying skin cells and further improve the skin'sown ability to absorb the hair growth components. In another embodiment,the method involves topical administration of the hair growth componentsin combination with an exfoliant and one or more moisturizing agents.Preferably, the method involves topical administration of the hairgrowth components in combination with an exfoliant, a hydrophilicmoisturizing agent, and a hydrophilic moisturizing agent. Withoutwishing to be bound by theory it is believed that the combination of anexfoliant, a hydrophilic moisturizing agent, and a hydrophobicmoisturizing agent interact in a synergistic manner to provide optimumconditions for absorption by the skin of topically applied hair growthcomponents.

The exfoliant may be an enzymatic exfoliant, or an acidic exfoliant. Anyenzymatic exfoliant known to those skilled in the art may be used in thecompositions and methods of the invention. Examples of enzymaticexfoliants useful in the compositions and methods of the inventioninclude, but are not limited to, papain, from papaya, and bromalein,from pineapple.

Examples of acidic exfoliants include, but are not limited to a mono- orpoly-hydroxy acid, tannic acid, or a mixture thereof, or apharmaceutically acceptable salt or ester thereof. One of ordinary skillin the art will be readily able to select and prepare suitable mono- orpoly-hydroxy acids for use in the composition of the invention, forexample, alkyl hydroxycarboxylic acids, aralkyl and arylhydroxycarboxylic acids, polyhydroxy-carboxylic acids, andhydroxy-polycarboxylic acids. One of ordinary skill in the art wouldtypically select one or more of the following mono- or -poly-hydroxyacids: 2-hydroxyacetic acid (glycolic acid); 2-hydroxypropanoic acid(lactic acid); 2-methyl 2-hydroxypropanoic acid; 2-hydroxybutanoic acid;phenyl 2-hydroxyacetic acid; phenyl 2-methyl 2-hydroxyacetic acid;3-phenyl 2-hydroxyacetic acid; 2,3-dihydroxypropanoic acid;2,3,4-trihydroxybutanoic acid; 2,3,4,5,6-pentahydroxyhexanoic acid;2-hydroxydodecanoic acid; 2,3,4,5-tetrahydroxypentanoic acid;2,3,4,5,6,7-hexahydroxyheptanoic acid; diphenyl 2-hydroxyacetic acid;4-hydroxymandelic acid; 4-chloromandelic acid; 3-hydroxybutanoic acid;4-hydroxybutanoic acid; 2-hydroxyhexanoic acid; 5-hydroxydodecanoicacid; 12-hydroxydodecanoic acid; 10-hydroxydecanoic acid;16-hydroxyhexadecanoic acid; 2-hydroxy-3-methylbutanoic acid;2-hydroxy-4-methylpentanoic acid; 3-hydroxy-4-methoxymandelic acid;4-hydroxy-3-methoxymandelic acid; 2-hydroxy-2-methylbutanoic acid;3-(2-hydroxyphenyl) lactic acid; 3-(4-hydroxyphenyl) lactic acid;hexahydromandelic acid; 3-hydroxy-3-methylpentanoic acid;4-hydroxydecanoic acid; 5-hydroxydecanoic acid; aleuritic acid;2-hydroxypropanedioic acid; 2-hydroxybutanedioic acid; erythraric acid;threaric acid; arabiraric acid; ribaric acid; xylaric acid; lyxaricacid; glucaric acid; galactaric acid; mannaric acid; gularic acid;allaric acid; altraric acid; idaric acid; talaric acid;2-hydroxy-2-methylbutanedioic acid; citric acid, isocitric acid,agaricic acid, quinic acid, glucoronic acid, glucoronolactone,galactoronic acid, galactoronolactone, uronic acids, uronolactones,ascorbic acid, dihydroascorbic acid, dihydroxytartaric acid, tropicacid, ribonolactone, gluconolactone, galactonolactone, gulonolactone,mannonolactone, citramalic acid; pyruvic acid, hydroxypyruvic acid,hydroxypyruvic acid phosphate and esters thereof; methyl pyruvate, ethylpyruvate, propyl pyruvate, isopropyl pyruvate; phenyl pyruvic acid andesters thereof; methyl phenyl pyruvate, ethyl phenyl pyruvate, propylphenyl pyruvate; formyl formic acid and esters thereof; methyl formylformate, ethyl formyl formate, propyl formyl formate; benzoyl formicacid and esters thereof; methyl benzoyl formate, ethyl benzoyl formateand propyl benzoyl formate; 4-hydroxybenzoyl formic acid and estersthereof; 4-hydroxyphenyl pyruvic acid and esters thereof; and2-hydroxyphenyl pyruvic acid and esters thereof.

In one embodiment the poly-hydroxy acidic components is an alpha-hydroxyacid. Preferred alpha-hydroxy acids include citric acid, glycolic acid,lactic acid. In another embodiment the poly-hydroxy acidic exfoliant isa beta-hydroxy acid. A preferred beta-hydroxy acid is salicylic acid.

It should be understood that one or more derivatives of the above acidiccomponent, such as esters or lactones thereof, are also suitably used.One of ordinary skill in the art will also understand that varioushydroxy acids described in U.S. Pat. Nos. 5,547,988 and 5,422,370 arealso suitable for use in the compositions and methods of the invention.The acidic component is present in the hair growth composition in anamount sufficient to exfoliate, i.e., remove dead or dying skin cells,from at least a portion of the skin. The acidic component, when includedin the hair growth composition, is typically present in an amount offrom about 0.1 to 12 weight percent, preferably from about 1 to 11weight percent, more preferably from about 4 to 10 weight percent of thehair growth composition. In one embodiment, the acidic component iscitric acid in an amount of from about 0.1 to 3 weight percent of thehair growth composition in combination with salicylic acid in an amountof up to about 2 weight percent of the hair growth composition.

Any route of administration can be used in the method of the invention.Suitable routes of administration include, but are not limited to, oral,topical rectal, parenteral, intravenous, transdermal, subcutaneous, andintramuscular. Although the method includes any suitable route ofadministration for providing the patient with an effective dosage of thehair growth components, topical and oral administration are preferred.Suitable dosage forms include tablets, troches, dispersions,suspensions, solutions, capsules, patches, suppositories, and the like,although oral and topical dosage forms are preferred.

It should be understood that the magnitude of a prophylactic ortherapeutic dose of the composition in the promotion of hair growth willvary with the severity of the condition to be treated and the route ofadministration. The dose, and perhaps the dose frequency, will also varyaccording to the age, body weight, and response of the individualpatient.

It is further recommended that children, patients aged over 65 years,and those with impaired renal or hepatic function initially receive lowdoses, and that they then be titrated based on individual response(s) orblood level(s). It may be necessary to use dosages outside the suggestedranges in some cases, as will be apparent to those of ordinary skill inthe art. Further, it is noted that the clinician or treating physicianwill know how and when to interrupt, adjust, or terminate therapy inconjunction with individual patient response.

The compositions used in the methods of the present invention includethe hair growth components and may also include pharmaceuticallyacceptable carriers, excipients and the like, and optionally, othertherapeutic ingredients.

The hair growth compositions for use in the methods of the presentinvention include compositions such as suspensions, solutions andelixirs; aerosols; or carriers such as starches, sugars,microcrystalline cellulose, diluents, granulating agents, lubricants,binders, disintegrating agents, and the like, in the case-of oral solidpreparations (such as powders, capsules, and tablets), with the oralsolid preparations being preferred over the oral liquid preparations.The most preferred oral solid preparations are tablets.

In one embodiment, the method involves oral administration of the hairgrowth components. Because of their ease of administration, tablets andcapsules represent the most advantageous oral dosage unit form, in whichcase solid pharmaceutical carriers are employed. If desired, tablets maybe coated by standard aqueous or nonaqueous techniques.

Pharmaceutical compositions for use in the methods of the presentinvention suitable for oral administration may be presented as discreteunits such as capsules, cachets, or tablets, or aerosol sprays, eachcontaining a predetermined amount of the active ingredient, as a powderor granules, as creams, pastes, gels, or ointments, or as a solution ora suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-wateremulsion, or a water-in-oil liquid emulsion. Such compositions may beprepared by any of the methods of pharmacy, but all methods include thestep of bringing into association the carrier with the active ingredientwhich constitutes one or more necessary ingredients. In general, thecompositions are prepared by uniformly and intimately admixing theactive ingredient with liquid carriers or finely divided solid carriersor both, and then, if necessary, shaping the product into the desiredpresentation.

For example, a tablet may be prepared by compression or molding,optionally, with one or more accessory ingredients. Compressed tabletsmay be prepared by compressing in a suitable machine the activeingredient in a free-flowing form such as powder or granules, optionallymixed with a binder, lubricant, inert diluent, surface active ordispersing agent. Molded tablets may be made by molding, in a suitablemachine, a mixture of the powdered compound moistened with an inertliquid diluent. Desirably, each tablet, cachet or capsule, contains fromabout 1 mg to 4,000 mg of the hair growth components, preferably about200 mg to 3,000 mg of the hair growth components, and more preferablyabout 600 mg to 2,000 mg of the of the hair growth components.

In another embodiment, the method involves topical administration of thehair growth components.

Suitable dosage forms for topical administration of the hair growthcomposition include, but are not limited to, dispersions; lotions;creams; gels; pastes; powders; aerosol sprays; syrups or ointments onsponges or cotton applicators; and solutions or suspensions in anaqueous liquid, non-aqueous liquid, oil-in-water emulsion, orwater-in-oil liquid emulsion. Because of its ease of administration, acream, lotion, or ointment represents the most advantageous topicaldosage form, in which case liquid pharmaceutical carriers may beemployed in the composition. These creams, lotions, or ointments, may beprepared as rinse-off or leave-on products, as well as two stagetreatment products for use with other skin cleansing or managingcompositions. In one embodiment, the hair growth compositions areadministered as a rinse-off product in a higher concentration form, suchas a gel, and then a leave-on product in a lower concentration to avoidirritation of the skin. Each of these forms is well understood by thoseof ordinary skill in the art, such that dosages may be easily preparedto incorporate the hair growth components of the invention.

In addition to the common dosage forms set out above, the compound foruse in the methods of the present invention may also be administered bycontrolled release means and/or delivery devices such as those describedin U.S. Pat. Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; and4,008,719, the disclosures of which are hereby incorporated byreference.

The hair growth compositions used in the methods of the invention may beprepared by any of the methods of pharmacy, but all methods include thestep of bringing into association the carrier(s) with the activeingredient, which constitutes one or more necessary ingredients. Ingeneral, the hair growth compositions are prepared by uniformly andintimately admixing the active ingredient with liquid carriers or finelydivided solid carriers or both, and then, if necessary, shaping theproduct into the desired presentation.

In another embodiment of the invention, the hair growth components canbe administered to the patient along with a second hair growth agent. Inone embodiment, the second hair growth agent is selected from minoxidil,procaine hydrochloride, niacin, pyrimidine 3-oxide compounds, ormixtures thereof.

EXAMPLES

The invention is further defined by reference to the following examplesdescribing in detail the preparation of hair growth compositions usefulin the methods of the invention, as well as their utility. The examplesare representative, and they should not be construed to limit the scopeof the invention.

Example 1 Capsules

A large number of unit capsules are prepared by filling standardtwo-piece hard gelatin capsules each with the desired amount of powderedhair growth components, 150 milligrams of lactose, 50 milligrams ofcellulose, and 6 milligrams magnesium stearate.

Example 2 Soft Gelatin Capsules

A mixture of hair growth components in a digestible oil such as soybeanoil, lecithin, cottonseed oil or olive oil is prepared and injected bymeans of a positive displacement pump into gelatin to form soft gelatincapsules containing the desired amount of the hair growth components.The capsules are washed and dried for packaging.

Example 3 Tablets

A large number of tablets were prepared by conventional procedures sothat the tablet unit included: the desired amount of the hair growthcomponents as described herein, 50 milligrams of red beet root powder,12 milligrams of stearic acid, 10.95 milligrams of sorbitol, 3milligrams of acdisol, 1 milligram of magnesium stearate, and 1milligram of syloid. Appropriate coatings may be applied to increasepalatability or delay absorption. A specific therapeutic formulation ofthe pharmaceutical composition described herein is set forth in thetable below:

Weight Percent Amount Chemical or Scientific Ingredient (% w/w) (mg)Name (if different) N-Acetylglucosamine 17.1 140 N-Acetyl D-GlucosamineVitamin C (81.2% 15 123.2 Ascorbic Acid) L-Lysine (80%) 12.2 100L-Lysine hydrochloride L-Proline 11 90 D-Glucosamine Sulfate 6.5 53.3(75%) Chondroitin Sulfate 6.1 50 (80%) Vitamin E Succinate 4.3 39.7 D-αtocopheryl acid succinate Zinc monomethionine 3.7 30 Zinc DL-methionine(20% Zn) N-Acetyl Cysteine 3.7 30 Manganese Ascorbate 2.8 23.1 (13% Mn)Vitamin B₃ Niacinamide 2.4 20 Niacinamide Quercetin Powder 2.4 20Quercetin dihydrate Grape Seed Extract 0.9 7.5 ProanthocyanidinPyridoxal 5 Phosphate- 0.6 5 P-5-P monohydrate Co B₆ Selenomethionine0.5 4 L-selenomethionine (0.5%) Vitamin A Palmitate 0.5 4 (500,000IU/GR) Copper Sebacate (14%) 0.4 2.9 Red beet root powder 6.1 50 Betavulgaris rubra Stearic acid 1.5 12 Sorbitol 1.3 11 Acdisol 0.4 3Microcrystalline cellulose Coconut oil 0.1 1 Magnesium stearate Syloid0.1 1 Silicon dioxide (amorphous) Total 100 820.7

These tablets are an example of a tablet useful in the methods of theinvention.

Example 4 Promotion of Hair Growth in Test Subjects

A 67 year-old female patient was administered the formulation describedin Example 3 at a dose of 2 tablets (1641.4 mg) per day. After 2 monthsthe patient reported increased hair growth on her toes and knees.

A 55 year-old female patient was administered the formulation describedin Example 3 at a dose of 2 tablets (1641.4 mg) per day. After 3 monthsthe patient reported increased hair growth on her toes.

A 40 year-old female patient was administered the formulation describedin Example 3 at a dose of 2 tablets (1641.4 mg) per day. After 3 monthsthe patient reported increased hair growth on her legs and forearms.

The present invention is not to be limited in scope by the specificembodiments disclosed in the examples which are intended asillustrations of a few aspects of the invention and any embodiments thatare functionally equivalent are within the scope of this invention.Indeed, various modifications of the invention in addition to thoseshown and described herein will become apparent to those skilled in theart and are intended to fall within the scope of the appended claims.

A number of references have been cited, the entire disclosures of whichare incorporated herein by reference in their entireties.

1. A method of promoting hair growth, which comprises: identifying anindividual suffering from hair loss, and administering to the individualan effective amount for promoting hair growth of: (1) a sugar compoundthat is converted to a glycosaminoglycan in the patient; (2) a primaryantioxidant component; (3) at least one amino acid component; (4) atleast one transition metal component, and (5) one or more componentsselected from the group consisting of lecithin, phosphatidyl choline,and choline, wherein the sugar compound is administered at a dose offrom about 40 mg to about 2500 mg per day; the primary antioxidant isadministered at a dose of from about 40 mg to about 2400 mg per day; theamino acid is administered at a dose of from about 35 mg to about 1200mg per day; and the transition metal component is administered at a doseof from about 4.1 mg to about 740 mg per day, and wherein the sugarcompound, the primary antioxidant component, the at least one amino acidcomponent, the at least one transition metal component, and the one ormore components selected from the group consisting of lecithin,phosphatidyl choline, and choline are administered simultaneously. 2.The method of claim 1, wherein the administration is topical.
 3. Themethod of claim 1, wherein the administration is oral.
 4. The method ofclaim 1, wherein the component is lecithin.
 5. The method of claim 1,wherein the component is phosphatidyl choline.
 6. The method of claim 1,wherein the component is choline.
 7. The method of claim 1, wherein thesugar compound that is converted to a glycosaminoglycan in the patientis N-acetylglucosamine or a salt or ester thereof; the primaryantioxidant component is ascorbic acid or a salt or ester thereof, theat least one amino acid is selected from the group consisting ofproline, lysine, cysteine, and methionine; and the transition metalcomponent is selected from the group consisting of zinc, manganese,copper, and mixtures thereof.
 8. The method of claim 1, furthercomprising administering a second hair growth agent.
 9. The method ofclaim 8, wherein the second hair growth agent is selected from the groupconsisting of minoxidil, procaine hydrochloride, niacin, pyrimidine3-oxide compounds, and mixtures thereof.